Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined mononuclear cell preparations from patients with chronic myeloid leukemia [CML] for binding of and response to 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]. Whole cells specifically took up [3H]-1,25-(OH)2D3 with high affinity (Kd 3.6 X 10(-11) M) and low capacity. Subcellular fractionation of labeled cells showed that binding was restricted to cytosols and nuclei. Sucrose gradient centrifugation of cells preincubated with [3H]-1,25-(OH)2D3 revealed a single 3.6S peak which was totally displaced with 100-fold excess nonradioactive hormone. However, we were unable to demonstrate specific binding of 1,25-(OH)2D3 by postlabeling standard cytosol preparations. In addition, cytosols prepared from a mixture of CML cells and 1,25-(OH)2D3 receptor-positive T47D (human breast cancer) cells had less than 10% of the binding measured in T47D cytosol alone. However, the levels of binding in T47D cytosols were not reduced if the receptors were occupied with [3H]-1,25-(OH)2D3 prior to the addition of the CML cytosols. Thus, CML cells appear to contain both the receptor for 1,25-(OH)2D3 and an unknown substance which prevents its detection following the preparation of cytosol. Cells from patients with CML in the chronic phase specifically bound more 1,25-(OH)2D3 [18.0 +/- 3.2 (S.E.) fmol/10(7) cells] than did those in acute myeloid transformation [7.2 +/- 1.5] or than did cells from patients with acute myeloid leukemia [2.6 +/- 0.8]. Only cells from the first group of patients responded to the addition of 1,25-(OH)2D3 by differentiating along the monocyte-macrophage pathway. We conclude that the differentiation-induction effect of 1,25-(OH)2D3 is likely to depend on adequate levels of receptor and that intact cells rather than cytosol preparations should be studied before cells of a particular tissue are designated as receptor negative.
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PMID:Specific uptake of 1,25-dihydroxycholecalciferol by human chronic myeloid leukemia cells. 633 55

1,25-Dihydroxyvitamin D3 inhibits the proliferation of the chronic myelogenous leukemia cell line RWLeu-4 but not the resistant variant, JMRD3. Although these cells exhibit no detectable differences in the vitamin D receptor, alterations in the interaction of nuclear extracts with the osteocalcin-1,25-dihydroxyvitamin D3-response element are noted. It is shown herein that the 1,25-dihydroxyvitamin D3 receptor binds to the osteocalcin-1,25-dihydroxyvitamin D3-response element along with activator protein-1 (AP-1) complexes and that the DNA binding activities of members of the Jun and Fos proto-oncogene families, which make up the AP-1 transcription factor, are differentially regulated by 1,25-dihydroxyvitamin D3. It is shown that JunD DNA binding activity is enhanced by 1,25-dihydroxyvitamin D3 during cell cycle arrest in the sensitive cells but is decreased in the resistant cells. These results suggest that the level of JunD DNA binding activity may be a critical factor in the regulation of proliferation.
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PMID:Differential regulation of JunD by dihydroxycholecalciferol in human chronic myelogenous leukemia cells. 764 76